Trial Outcomes & Findings for Effects of Anorexia Nervosa on Bone Mass in Adolescents (NCT NCT00088153)
NCT ID: NCT00088153
Last Updated: 2021-11-02
Results Overview
Bone density at the spine (lumbar 1-4 vertebrae) was measured using dual energy x-ray absorptiometry (DXA) at baseline, 6 months, 12 months and 18 months. The primary outcome was the percent change in bone density at the spine from baseline to 18 months. Areal bone density is measured as g/cm2. The unit of measure for the percent change in bone density is 'percent' Percent change in bone density= \[\[Bone density at 18 months- Bone density at baseline)\*100/Bone density at baseline\]%
Recruitment status
COMPLETED
Study phase
PHASE2/PHASE3
Target enrollment
110 participants
Primary outcome timeframe
Baseline and 18 months
Results posted on
2021-11-02
Participant Flow
Period of recruitment: 2003-2009. Location: Massachusetts General Hospital (Boston) and Hospital for Sick Children (Toronto). We screened 150 girls with anorexia nervosa (AN) (110 at MGH and 40 at SickKids) and 88 normal-weight controls 12-18 years. Following the screen, 110 AN and 40 controls were enrolled for the prospective study.
Reasons for enrolled participants being excluded from the trial before assignment to groups primarily included identification of exclusion criteria, loss of interest on the part of the participant, and loss to follow-up.
Participant milestones
| Measure |
Physiologic Estrogen Replacement
Mature girls with anorexia nervosa (bone age 15 or greater): Transdermal estradiol (100 mcg) with cyclic progesterone (days 1-10 of each month).
Immature girls with anorexia nervosa (bone age less than 15 years): Ethinyl estradiol (3.75 mcg daily for the first 6 months, 7.5 mcg daily for the next 6 months, and 11.25 mcg daily for the final 6 months of the study
|
Placebo
Mature girls with anorexia nervosa with a bone age of 15 years of greater: Placebo patches; Immature girls with anorexia nervosa with a bone age of less than 15 years: Placebo pills
|
|---|---|---|
|
Overall Study
STARTED
|
55
|
55
|
|
Overall Study
COMPLETED
|
31
|
30
|
|
Overall Study
NOT COMPLETED
|
24
|
25
|
Reasons for withdrawal
| Measure |
Physiologic Estrogen Replacement
Mature girls with anorexia nervosa (bone age 15 or greater): Transdermal estradiol (100 mcg) with cyclic progesterone (days 1-10 of each month).
Immature girls with anorexia nervosa (bone age less than 15 years): Ethinyl estradiol (3.75 mcg daily for the first 6 months, 7.5 mcg daily for the next 6 months, and 11.25 mcg daily for the final 6 months of the study
|
Placebo
Mature girls with anorexia nervosa with a bone age of 15 years of greater: Placebo patches; Immature girls with anorexia nervosa with a bone age of less than 15 years: Placebo pills
|
|---|---|---|
|
Overall Study
Physician Decision
|
3
|
3
|
|
Overall Study
Withdrawal by Subject
|
10
|
10
|
|
Overall Study
Lost to Follow-up
|
11
|
12
|
Baseline Characteristics
Effects of Anorexia Nervosa on Bone Mass in Adolescents
Baseline characteristics by cohort
| Measure |
Physiologic Estrogen Replacement
n=55 Participants
Mature girls with anorexia nervosa (bone age 15 or greater): Transdermal estradiol (100 mcg) with cyclic progesterone (days 1-10 of each month).
Immature girls with anorexia nervosa (bone age less than 15 years): Ethinyl estradiol (3.75 mcg daily for the first 6 months, 7.5 mcg daily for the next 6 months, and 11.25 mcg daily for the final 6 months of the study
|
Placebo
n=55 Participants
Mature girls with anorexia nervosa with a bone age of 15 years of greater: Placebo patches; Immature girls with anorexia nervosa with a bone age of less than 15 years: Placebo pills
|
Total
n=110 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
55 Participants
n=5 Participants
|
55 Participants
n=7 Participants
|
110 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
16.6 years
STANDARD_DEVIATION 1.6 • n=5 Participants
|
16.3 years
STANDARD_DEVIATION 1.6 • n=7 Participants
|
16.5 years
STANDARD_DEVIATION 0.2 • n=5 Participants
|
|
Sex: Female, Male
Female
|
55 Participants
n=5 Participants
|
55 Participants
n=7 Participants
|
110 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
55 participants
n=5 Participants
|
55 participants
n=7 Participants
|
110 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and 18 monthsPopulation: The number of participants was determined using power calculations based on preliminary data. For our primary longitudinal analysis, bone mineral density (BMD) changes were analyzed using a mixed model analysis of variance (intent-to-treat model). For secondary analysis, we examined BMD changes after controlling for age and weight changes.
Bone density at the spine (lumbar 1-4 vertebrae) was measured using dual energy x-ray absorptiometry (DXA) at baseline, 6 months, 12 months and 18 months. The primary outcome was the percent change in bone density at the spine from baseline to 18 months. Areal bone density is measured as g/cm2. The unit of measure for the percent change in bone density is 'percent' Percent change in bone density= \[\[Bone density at 18 months- Bone density at baseline)\*100/Bone density at baseline\]%
Outcome measures
| Measure |
Physiologic Estrogen Replacement
n=55 Participants
Mature girls with anorexia nervosa (AN) (bone age ≥15 years) randomized this arm received transdermal 17-β estradiol (100 mcg patch applied twice weekly) continuously over the study duration. Girls randomized to the active estradiol patch also received medroxyprogesterone 2.5 mg daily for 10 days each month. Immature girls with AN (bone age\<15 years, N=14) randomized to this arm received escalating doses of oral ethinyl estradiol (3.75 mcg daily for the first 6 months, 7.5 mcg daily for the second 6 months, and 11.25 mcg daily for the last 6 months). All subjects were given 1200 mg calcium carbonate and 400 IU vitamin D daily.
|
Placebo
n=55 Participants
Mature girls with anorexia nervosa (AN) randomized to this arm received placebo patches and cyclic placebo pills.
Immature girls with AN randomized to this arm received placebo pills. All subjects received supplemental calcium (1200 mg) and vitamin D (400 IU) daily
|
|---|---|---|
|
Percent Change in Spine Bone Density Over the Study Duration (18 Months)
|
2.6 Percent change
Standard Deviation 1.0
|
0.3 Percent change
Standard Deviation 0.1
|
PRIMARY outcome
Timeframe: Baseline and 18 monthsBone density at the spine (lumbar 1-4 vertebrae) was measured using dual energy x-ray absorptiometry (DXA) at baseline, 6 months, 12 months and 18 months. The other primary outcome was the change in spine bone density Z-score from baseline to 18 months. The bone density Z-score is a standard deviation score that compares one's bone density to the mean for age and gender, and the Z-score, therefore, does not have any units. It is simply referred to as a Z-score. Change in bone density Z-score= \[Bone density Z-score at 18 months- Bone density Z-score at baseline\]
Outcome measures
| Measure |
Physiologic Estrogen Replacement
n=55 Participants
Mature girls with anorexia nervosa (AN) (bone age ≥15 years) randomized this arm received transdermal 17-β estradiol (100 mcg patch applied twice weekly) continuously over the study duration. Girls randomized to the active estradiol patch also received medroxyprogesterone 2.5 mg daily for 10 days each month. Immature girls with AN (bone age\<15 years, N=14) randomized to this arm received escalating doses of oral ethinyl estradiol (3.75 mcg daily for the first 6 months, 7.5 mcg daily for the second 6 months, and 11.25 mcg daily for the last 6 months). All subjects were given 1200 mg calcium carbonate and 400 IU vitamin D daily.
|
Placebo
n=55 Participants
Mature girls with anorexia nervosa (AN) randomized to this arm received placebo patches and cyclic placebo pills.
Immature girls with AN randomized to this arm received placebo pills. All subjects received supplemental calcium (1200 mg) and vitamin D (400 IU) daily
|
|---|---|---|
|
Change in Spine Bone Mineral Density Z-scores Over the Study Duration (18 Months)
|
-0.026 Z -scores
Standard Deviation 0.078
|
-0.236 Z -scores
Standard Deviation 0.091
|
SECONDARY outcome
Timeframe: Baseline and 18 monthsPopulation: The number of participants was determined based on our preliminary data. This analysis was based on completers only.
P1NP is a surrogate marker of bone formation that is measured in serum. P1NP levels were measured at baseline, 6, 12 and 18 months. A secondary outcome was the change in P1NP levels from baseline to 18 months: \[P1NP at 18 months - P1NP at baseline). The unit is ng/ml
Outcome measures
| Measure |
Physiologic Estrogen Replacement
n=55 Participants
Mature girls with anorexia nervosa (AN) (bone age ≥15 years) randomized this arm received transdermal 17-β estradiol (100 mcg patch applied twice weekly) continuously over the study duration. Girls randomized to the active estradiol patch also received medroxyprogesterone 2.5 mg daily for 10 days each month. Immature girls with AN (bone age\<15 years, N=14) randomized to this arm received escalating doses of oral ethinyl estradiol (3.75 mcg daily for the first 6 months, 7.5 mcg daily for the second 6 months, and 11.25 mcg daily for the last 6 months). All subjects were given 1200 mg calcium carbonate and 400 IU vitamin D daily.
|
Placebo
n=55 Participants
Mature girls with anorexia nervosa (AN) randomized to this arm received placebo patches and cyclic placebo pills.
Immature girls with AN randomized to this arm received placebo pills. All subjects received supplemental calcium (1200 mg) and vitamin D (400 IU) daily
|
|---|---|---|
|
Change in N-terminal Propeptide of Type 1 Procollagen (P1NP) Over the Study Duration (18 Months)
|
-2.9 ng/ml
Standard Deviation 22.5
|
-10.9 ng/ml
Standard Deviation 27.0
|
Adverse Events
Physiologic Estrogen Replacement
Serious events: 12 serious events
Other events: 18 other events
Deaths: 0 deaths
Placebo
Serious events: 16 serious events
Other events: 20 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Physiologic Estrogen Replacement
n=55 participants at risk
Mature girls with anorexia nervosa (bone age 15 or greater): Transdermal estradiol (100 mcg) with cyclic progesterone (days 1-10 of each month).
Immature girls with anorexia nervosa (bone age less than 15 years): Ethinyl estradiol (3.75 mcg daily for the first 6 months, 7.5 mcg daily for the next 6 months, and 11.25 mcg daily for the final 6 months of the study
|
Placebo
n=55 participants at risk
Mature girls with anorexia nervosa with a bone age of 15 years of greater: Placebo patches; Immature girls with anorexia nervosa with a bone age of less than 15 years: Placebo pills
|
|---|---|---|
|
General disorders
Hospitalizations for low weight and/or bradycardia
|
21.8%
12/55 • Number of events 12 • 18 months for each subject(AN E+ versus AN E-)
|
29.1%
16/55 • Number of events 16 • 18 months for each subject(AN E+ versus AN E-)
|
|
Reproductive system and breast disorders
Increased vaginal bleeding
|
1.8%
1/55 • Number of events 1 • 18 months for each subject(AN E+ versus AN E-)
|
0.00%
0/55 • 18 months for each subject(AN E+ versus AN E-)
|
|
Skin and subcutaneous tissue disorders
Erythema at patch application site
|
0.00%
0/55 • 18 months for each subject(AN E+ versus AN E-)
|
1.8%
1/55 • Number of events 1 • 18 months for each subject(AN E+ versus AN E-)
|
|
Reproductive system and breast disorders
Pregnancy
|
0.00%
0/55 • 18 months for each subject(AN E+ versus AN E-)
|
1.8%
1/55 • Number of events 1 • 18 months for each subject(AN E+ versus AN E-)
|
|
Psychiatric disorders
Suicidal ideation
|
1.8%
1/55 • Number of events 1 • 18 months for each subject(AN E+ versus AN E-)
|
1.8%
1/55 • Number of events 1 • 18 months for each subject(AN E+ versus AN E-)
|
Other adverse events
| Measure |
Physiologic Estrogen Replacement
n=55 participants at risk
Mature girls with anorexia nervosa (bone age 15 or greater): Transdermal estradiol (100 mcg) with cyclic progesterone (days 1-10 of each month).
Immature girls with anorexia nervosa (bone age less than 15 years): Ethinyl estradiol (3.75 mcg daily for the first 6 months, 7.5 mcg daily for the next 6 months, and 11.25 mcg daily for the final 6 months of the study
|
Placebo
n=55 participants at risk
Mature girls with anorexia nervosa with a bone age of 15 years of greater: Placebo patches; Immature girls with anorexia nervosa with a bone age of less than 15 years: Placebo pills
|
|---|---|---|
|
Gastrointestinal disorders
Nausea/vomiting
|
25.5%
14/55 • Number of events 14 • 18 months for each subject(AN E+ versus AN E-)
|
14.5%
8/55 • Number of events 8 • 18 months for each subject(AN E+ versus AN E-)
|
|
Vascular disorders
Dizziness
|
10.9%
6/55 • Number of events 6 • 18 months for each subject(AN E+ versus AN E-)
|
18.2%
10/55 • Number of events 10 • 18 months for each subject(AN E+ versus AN E-)
|
|
Nervous system disorders
Headaches
|
18.2%
10/55 • Number of events 10 • 18 months for each subject(AN E+ versus AN E-)
|
25.5%
14/55 • Number of events 14 • 18 months for each subject(AN E+ versus AN E-)
|
|
Gastrointestinal disorders
Bloating
|
32.7%
18/55 • Number of events 18 • 18 months for each subject(AN E+ versus AN E-)
|
29.1%
16/55 • Number of events 16 • 18 months for each subject(AN E+ versus AN E-)
|
|
Gastrointestinal disorders
Constipation
|
7.3%
4/55 • Number of events 4 • 18 months for each subject(AN E+ versus AN E-)
|
7.3%
4/55 • Number of events 4 • 18 months for each subject(AN E+ versus AN E-)
|
|
Reproductive system and breast disorders
Breast tenderness
|
25.5%
14/55 • Number of events 14 • 18 months for each subject(AN E+ versus AN E-)
|
16.4%
9/55 • Number of events 9 • 18 months for each subject(AN E+ versus AN E-)
|
|
Reproductive system and breast disorders
Increased vaginal discharge
|
23.6%
13/55 • Number of events 13 • 18 months for each subject(AN E+ versus AN E-)
|
16.4%
9/55 • Number of events 9 • 18 months for each subject(AN E+ versus AN E-)
|
|
Reproductive system and breast disorders
Increased uterine bleeding
|
23.6%
13/55 • Number of events 13 • 18 months for each subject(AN E+ versus AN E-)
|
16.4%
9/55 • Number of events 9 • 18 months for each subject(AN E+ versus AN E-)
|
|
Eye disorders
Irritation from contact lenses
|
3.6%
2/55 • Number of events 2 • 18 months for each subject(AN E+ versus AN E-)
|
10.9%
6/55 • Number of events 6 • 18 months for each subject(AN E+ versus AN E-)
|
|
Skin and subcutaneous tissue disorders
Perceived increase in facial hair
|
5.5%
3/55 • Number of events 3 • 18 months for each subject(AN E+ versus AN E-)
|
1.8%
1/55 • Number of events 1 • 18 months for each subject(AN E+ versus AN E-)
|
|
Skin and subcutaneous tissue disorders
Perceived loss of scalp hair
|
14.5%
8/55 • Number of events 8 • 18 months for each subject(AN E+ versus AN E-)
|
9.1%
5/55 • Number of events 5 • 18 months for each subject(AN E+ versus AN E-)
|
|
Psychiatric disorders
Worsening depression
|
5.5%
3/55 • Number of events 3 • 18 months for each subject(AN E+ versus AN E-)
|
9.1%
5/55 • Number of events 5 • 18 months for each subject(AN E+ versus AN E-)
|
|
Skin and subcutaneous tissue disorders
Erythema at patch application site
|
30.9%
17/55 • Number of events 17 • 18 months for each subject(AN E+ versus AN E-)
|
34.5%
19/55 • Number of events 19 • 18 months for each subject(AN E+ versus AN E-)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place